Benzylic enolate anions

FORMATION AND ALKYLATION OF SPECIFIC ENOLATE ANIONS FROM AN UNSYMMETRICAL KETONE 2-BENZYL-2-METHYLCY-CL0HEXAN0NE AND 2-BENZYL— 6-METHYLCYCLOHEXANONE, 52,... 

In neutral medium A16-, A17(20)-, and A20-olefins are hydrogenated over palladium in preference to the double bonds of A4-3-ketones.67 The double bonds of A4-3-ketones and A16-20-ketones are reduced in preference to A5-,93 A7-48 155 and A9(I -olefins.2 169 The double bond of a A14-16-ketone is saturated before a 5-ene.70,163 In basic medium the carbonyl conjugated double bond is preferentially saturated in all cases92 presumably because of the strong adsorption of the enolate anion (see section II-C). Debromination (9a-bromo 11-ketone) occurs before saturation of the A4-3-keto double bond14 over Raney nickel but hydrogenation of benzyl ethers takes place concurrently with the hydrogenation of this double bond over palladium in neutral medium.96... 

Enolate anions 54, which can be generated from peri-acyl-oxy-substituted naphthyl benzyl ketones 52 or from their enolacylates 53, undergo rearrangement into 5-methoxynaphtholactone 48 or 2-benzyl-... 

Gall, M. House, H. O. The formation and alkylation of specific enolate anions from an unsymmetrical ketone 2-benzyl-2-methylcy-clohexanone and 2-benzyl-6-methylcyclohexa-none. Org. Synth. 1988, Coll. Vol. VI, 121-130. 

The normal U-shaped Hammett plots were found for both the catalysed [by a copper(II)salen complex (31)] and uncatalysed asymmetric alkylation of enolates by substituted benzyl bromides,126 indicating that both reactions occur via an. S N2 mechanism (Scheme 15). Because both reactions were faster when electron-withdrawing substituents were on the benzyl bromide, it was concluded that there was more bond formation than bond rupture in the. S N2 transition states. Because the curvature of the Hammett plot was greater for the catalysed reaction, it was concluded that the catalysed reaction has a later transition state with a greater negative charge on Ca. The role of the catalyst was to increase the nucleophilic character of the enolate anion. 

The family of photoreducible dyes (e.g, acridinium, xanthene, thiazinium among other classes of dyes) produce excited states of essentially quinoidal structures which can act as efficient acceptors of electrons. Amines [59], sulfur compounds, especially sulfmate salts [60], heterocycles of low ionization potential [61], alkylcarboxylates and stable enolate anions [62], and several classes of organo-metallic compounds, notably allylic and benzylic organostannanes [63], represent classes of compounds which have proved efficacious as coinitiators in electron transfer sensitization with these dyes. Electron transfer with the organometallics was unambiguously established in a series of model studies involving electron acceptors of the anthracene class [64],... 

The enolate anions of 2-acetylthiophene and 2-acetylfuran have been arylated under photochemical conditions in the presence of t-BuOK and good electron donors such as acetone enolate (entrainment reaction) to give the corresponding benzyl 2-thienyl and 2-furanyl ketones respectively. Use of FeBr2 as initiator in a dark reaction gives good yields of the substitution products without the need for added nucleophiles, and it is suggested that these arylation processes occur by an SrnI mechanism. 

The a-protons that are less sierically hindered are most rapidly removed by a bulky base. Thus, addition of an unsymmetrical ketone to an excess of lithium diisopropy-lamide (LDA) gives the enolate anion on the less substituted side as the result of kinetic control. 2-Methylcyclohe anone has been specifically benzylated in the (3-position in this manner [4],... 

That s the Fischer indole synthesis. The Reissert synthesis in some respects is more straightforward. The first step is a distant relative of a Claisen condensation, but a (nitro-group stabilized) benzylic anion takes the place of an enolate anion to add to the carbonyl group of the ester as shown ... 

Alkylation of enolate anions is achieved readily with alkyl halides or other alkylating agents. Both primary and secondary alkyl, allyl or benzyl halides may be used successfully, but with tertiary halides poor yields of alkylated product often result because of competing elimination. It is sometimes advantageous to proceed by way of the toluene-p-sulfonate, methanesulfonate or trifluoromethane-sulfonate rather than a halide. The sulfonates are excellent alkylating agents and can usually be obtained from the alcohol in a pure condition more readily than... 

This reaction, described by the authors as a Diels-Alder cycloaddition via the o-xylylene (p. 99), was employed in carbohydrate chemistry to produce anthra-cyclinone analoguesNq reaction occurs without sonication. The mechanism was not established with certainty, and it can be postulated that a mono-organozinc reagent adds to the activated olefin and the enolate anion undergoes an alkylation from the second benzylic bromide. 

Draw the product formed when the enolate anion of cyclopen-tanone reacts with 4i2-benzyl-2i2-iodoheptane. 

A variation of the malonic ester synthetic uses a P-keto ester such as 116. In Section 22.7.1, the Claisen condensation generated P-keto esters via acyl substitution that employed ester enolate anions. When 116 is converted to the enolate anion with NaOEt in ethanol, reaction with benzyl bromide gives the alkylation product 117. When 117 is saponified, the product is P-keto acid 118, and decarboxylation via heating leads to 4-phenyl-2-butanone, 119. This reaction sequence converts a P-keto ester, available from the ester precursors, to a substituted ketone in what is known as the acetoacetic acid synthesis. Both the malonic ester synthesis and the acetoacetic acid synthesis employ enolate alkylation reactions to build larger molecules from smaller ones, and they are quite useful in synthesis. 

Ethers are relatively unreactive and will not react in an acyl addition reaction or with the reactions of enolate anions. However, when a benzyl ether is treated with hydrogen gas and a palladium catalyst, hydrogenolysis leads to 2-butanol and toluene (see Chapter 19, Sections 19.3.4,19.3.5, and Chapter 21, Section 21.6, for hydrogenolysis). The benzyl ether is a good projecting group for an alcohol and a few other ethers may also be used. 

In Chapter 22 (Section 22.7.4), malonate derivatives were easily converted to the corresponding enolate anion, and reaction with alkyl halides or other electrophilic species gave the C3-alkylated product. Indeed, if 102 is treated with sodium metal (or NaH, LDA, etc.), enolate anion 103 is formed it reacts with an alkyl halide such as benzyl bromide (PhCH2Br) to give 104. If 104 is heated with aqueous sodium hydroxide and then treated with aqueous HCI, phthalic acid (35) and the amino acid phenylalanine (57) are formed as the final products. 

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